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Comment by Aurornis | Hacker News Reader

LDL is a proxy measure that's cheap and easy to measure. It's widely used for screening despite not being perfect, which confused some into thinking it's the one and only thing measure of CVD risk. It's not, though. Many of the tests we look at are proxies and markers, not actually the sole factor for a disease.

More in-depth testing would check LDL-P (particle count) and ApoB along with hsCRP.

Though realistically, most people could simply look at their diet and lifestyle and work on improving both before investing in any extra testing. The testing can be useful to catch cases where genetics overwhelm even healthy lifestyles, but in many cases for younger people the testing basically serves as a wake-up call to actually do something about lifestyle and diet problems. It's easier to inspire lifestyle and diet changes when you're staring at bad numbers on the test results and getting a little preview of the consequences of your decisions.

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My cholesterol is (frankly) through the roof. My GP wanted to start statins immediately. I pushed back and asked what the big deal was -- my RHR is low, BP is normal, my weight is fine, I have an active lifestyle, and my diet is fine. They explained that the cholesterol might build up a blockage in my heart, and that higher levels meant higher increased risk of that. So I asked whether we could just check and see if that's actually happening, and you can! It's a calcium scoring test, and it cost me $150.

I got a zero, in other words, no blockage at all. When I reviewed my results with a cardiologist, he basically said, "Some people just have high cholesterol, and it's not a problem. You're probably one of them." I also separately got tested for the type of LDL particles, and mine were primarily composed of big, floaty ones that aren't associated with increased risk (or at least that's what the test result notes said).

I'll do the calcium score every 5 years just to keep tabs on it. But thankfully I didn't start a needless medication regimen.

Same story here (though it cost me more - insurance refused to cover it because I did not meet the criteria [0])

LDL while clearly not telling the whole story is a great first line defense at population levels because it's easy and cheap (similar to BMI). If you just throw Statins at everybody with high LDL you're going to improve health outcomes, and historically providers and researchers have considered statins to be effectively "free" (both in actual cost and in side effects).

In developed countries where the equipment for this test is readily available, individual patients should absolutely request it even if paying out of pocket, if for nothing more than their own peace of mind.

I'm a layman but I have come to conclude that the AHA's guidelines on when to recommend the CAC test are too conservative. Definitive knowledge of the underlying pathology (or lack thereof) seems like it would be useful both for people with exceptionally high and exceptionally low scores. Even if in a vast majority of cases the treatment plan would be similar (just give them statins) more knowledge seems better on an individual treatment level.

[0] https://www.heart.org/en/health-topics/heart-attack/diagnosi...

Calcium scores only reflect calcified plaque - not soft plaque. CTTA is what you need for that.

Particularly for people below ~45 with significant plaque buildup, calcium scores are often 0 or very low, because all of the plaque is soft.

This is one of the reasons CACs aren't used much in younger people - that plaque hasn't yet calcified.

Soft plaque is the dangerous stuff, too - most statins actually calcify plaque, but this stabilizes it and prevents it from rupturing and the chunks entering the bloodstream.

Thanks for the info! I'll look into this for my next checkup.

Calcium scores only show calcified plaque - not soft. You need a CTTA for that.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10920137

You're probably a "lean mass hyper-responders", a phenotype which is actively investigated, initial paper:

Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research

https://pubmed.ncbi.nlm.nih.gov/36351849/

A few other more recent papers:

https://pubmed.ncbi.nlm.nih.gov/35498420/

https://www.jacc.org/doi/10.1016/j.jacadv.2024.101109

Note: I'm not a doctor.

Wow, this might actually be me. When I was doing a protein-heavy, carb-light diet, my numbers matched up with these ranges exactly. High LDL, high HDL over 80, and low triglycerides. Granted that was a good 15 years ago, but still. Glad to have something specific to look for.

You're missing a key fact, which others have noted, but I would phrase it differently.

Calcium is the end-stage of atherosclerosis. In other words, only advanced atherosclerosis has calcium. The electron beam CT test can, therefore, read zero in people with extensive atherosclerosis, if it is still in the earlier stages. As others note, even early atherosclerosis is bad.

That is why insurance doesn't cover electron beam CT -- it's a crappy test. It provides no reassurance if it's negative, and on a population scale the LDL is far more cost effective and convenient to identify people who need statins.

You might look back at studies from the early statin days, like AFCAPS/TexCAPS, which looked at healthy people like you, whose only risk factor was high cholesterol. The ones who got even the primitive statins of the day lowered their risk of a first coronary event by 37%. That doesn't even tell the whole story, because atherosclerosis can affect any artery in the body. You want your kidneys, eyes, ears, brain, legs, and penis (when present) to work well to the end of your days. Atherosclerosis is a terrible disease.

LDL is almost always talked about as a singluar thing, even in scientific studies when LDL comes in several flavors.

Large bouyant LDL is not associated with CVD risk whereas small dense LDL is.

You can have high HDL, high LDL and low triglycerides. This is a pretty rare pattern, but one where you do not have increase risk of CVD.

In most people, having high LDL is linked to having high small dense LDL and low aounts of large boyant LDL. Hence why LDL is used as a simple risk measure - even though it's wrong.

Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.

This doesn't really seem to pan out in reality. Often people with small dense LDL have it as a result of other risk markers. There's a good discussion here - https://www.youtube.com/watch?v=kplh30RmYo8 - the long and short of it is that when you perform mutual adjustment for number of particles, both large and small LDL particles are associated with a fairly similar risk. But if you have the same mass of cholesterol in two individuals (LDL-c) and one has SD LDL and the other has LB LDL, the latter has fewer LDL particles and therefore lower risk, so it can appear that LB LDL are less risky if you're only measuring cholesterol mass.

As for statins not working well in primary prevention, I'm not sure what you mean - the JUPITER trial showed significant risk reductions for primary prevention, for example.

The Jupiter trial clearly stated that those with low hs-crp didn’t benefit from LDL-C reduction, only those with high hs-crp had reduced CVD events due to LDL-C reduction.

The claim I was addressing was that we don’t have evidence of statin efficacy for primary prevention. My point was that JUPITER seems to be evidence this isn’t the case.

PCSK9 inhibitor trials have shown significant benefit for reduction in CVD events independent of whether or not the inhibitors lowered hsCRP. Ezetimibe makes an impact on events without reducing hsCRP when administered on it's own. (But it is generally administered with a statin, and it seems that the combination does result in lower hsCRP than a statin on it's own)

https://pmc.ncbi.nlm.nih.gov/articles/PMC4876179/ https://pubmed.ncbi.nlm.nih.gov/36779348/

> Statins in trials show benefits for secondary events, but for primary protection statins don't actually work that well.

This just simply isn't true and we have massive quantities of data pointing towards protection against major vascular events - even in people that we previously would have considered as having "normal" cholesterol. The NLA and AHA has been revising their guidelines to start getting people on statins sooner and to get levels lower for a reason - it works.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

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